A tragic irony exists in modern medicine. Amidst the vast progress we’ve made against complex illnesses such as heart disease, cancer and diabetes, infections have reemerged as a major public health threat.

More than 1.7 million people acquire bacterial infections in U.S. hospitals annually, and 99,000 die as a result [1]. These numbers are alarming and the causes are complex, but we do know that much of it is related to bacterial resistance to current drugs. About 70% of the bacteria that cause bloodstream or lung infections in the hospital have developed resistance to at least one antimicrobial drug. [2] Moreover, some pathogens are gaining ground. For instance, Clostridium difficile killed approximately 6,300 people in 2007, eight times more than it did in 1999 [3].

Our repertoire of antibiotics is waning in efficacy and it is vital that we develop new medicines. The company for which we work – Cubist Pharmaceuticals – is one of only a handful of biopharmaceutical companies that continues to discover, develop and make available new antibiotics. This is in stark contrast to 1990, when nearly 20 biopharmaceutical companies had large antibiotic research and development (R&D) programs [4].

What happened? The antibiotic pipeline is running dry because antibiotics have come to be viewed by many drug makers as “wasting assets.”
Each new antibiotic likely has a finite lifespan, because the quick evolution of bacteria makes development of resistance inevitable. To preserve their effectiveness for the future, it is common practice to reserve new agents as a last line of defense. This situation paradoxically reduces the commercial returns that a company needs to overcome escalating investment costs in R&D that lead to new medicines approved by the U.S. Food and Drug Administration (FDA). Recent estimates place R&D costs from $800 million to $1.7 billion, and the time commitment is more than a decade to bring a new drug to market [3,5]. Without new medicines, doctors and patients are forced to rely on the currently available antibiotics, and sometimes, they encounter infections due to pathogens that are not susceptible to any such antibiotics.

This vicious cycle has caused many drug makers to abandon antibiotic R&D programs in favor of those for chronic diseases that have a greater potential for long-term financial return. After all, the goal in addressing infections is to use a short treatment course to cure patients as quickly as possible.

One mechanism to help overcome some of the challenges that are paralyzing antibiotic development is approval of the Generating Antibiotic Incentives Now (GAIN) Act. This bipartisan public health measure would undoubtedly help to spur innovation of new anti-infective drugs and diagnostics.
The GAIN Act would extend marketing protection for select “qualified infectious disease products” that significantly improve our ability to fight infections caused by resistant pathogens. The bill also provides for additional exclusivity for those medicines developed with a companion diagnostic test, thus encouraging personalized medicine and thereby optimizing appropriate antibiotic use. It also assures that new types of antibiotics are eligible for expedited review under existing programs at the FDA (Priority Review and Fast Track Status). Finally, the Act calls for the FDA to revise its guidelines for antibiotic clinical trials to reflect the latest developments in science and clinical knowledge.

Another avenue is for stakeholders to work with the FDA to advance regulatory science in this important area. One interesting idea was recently set forth by the Infectious Diseases Society of America (IDSA) – a network of nearly 10,000 infectious diseases doctors and scientists.

The IDSA proposed that the FDA consider a special regulatory pathway for new antibiotics that balances the need to make them quickly available with maintaining the required oversight to ensure these medicines are safe and effective [6]. The idea is modeled on the successful Orphan Drug Act for rare diseases and warrants thoughtful consideration by FDA officials.

The IDSA has also issued guidelines to help doctors make the best treatment decisions for their patients based on the latest science [7]. Aside from the medical benefit, preventing relapse may also reduce the cost-burden of hospital acquired infections. It is estimated that resistant infections account for an estimated $35 billion in additional costs from longer and more complex treatments [8].

Over the past 30 years we have made tremendous progress against modern causes of human mortality - heart attacks, strokes and cancer. However, we should not forget that human history is peppered with bouts of plagues and pestilence. One must consider, what good is it to perform a life-saving organ transplant only to lose that life to an infection due to a multidrug-resistant pathogen? It will take the collective effort of government, healthcare providers, and the biopharmaceutical industry to ensure development of new antimicrobials and preservation of existing antimicrobials in hopes that we do not have to answer such questions.